JP6064156B2 - Deep body temperature raising agent - Google Patents

Description

  The present invention relates to an agent for increasing deep body temperature.

  The body temperature of a living body can be broadly divided into a deep body temperature that represents the temperature of the deep body and a body surface temperature that represents the temperature of the body surface.

  When the temperature inside and outside the body rises, heat inside the body is dissipated outside the body due to sweating or skin vasodilation, and conversely, when the temperature inside and outside the body falls, the skin blood vessels contract or shake to produce heat. Therefore, the body surface temperature is likely to change under the influence of the environment and the like. In contrast, deep body temperature plays a fundamental role in the normal functioning of various physiological responses in the living body, and homeostasis maintains homeostasis. On the other hand, deep body temperature also has a circadian rhythm in which it rises during the day and falls at night.

  Usually, the normal human body temperature is 36-37 ° C. With this body temperature, the immune function works actively and health can be maintained. However, in recent years, the number of people with hypothermia has also increased due to the effects of smoking, excessive stress, lack of exercise, lack of sleep, unreasonable diet, and cooling. When the body temperature decreases, metabolic function decreases, and the subjective symptoms are cold, and lower limb edema, body malaise, etc. appear. In general, it is said that when the average body temperature decreases by 1 ° C., the immunity decreases by about 37%. On the other hand, it is said that when the average body temperature increases by 1 ° C., the immunity is activated about 60%.

  In general, coldness refers to “a symptom that the limbs and hips always feel cold. And the constitution.” It is mainly due to autonomic disturbance, hormonal imbalance, hypotension, and anemia. The adjustment of the surface temperature is unsatisfactory, but the phenomenon is different from “hypothermia” and “cold” here, and the countermeasures are also different.

  Conventionally, in order to raise deep body temperature and improve immune function, exercise has been tried, massage and diet improvement, Chinese medicine intake, etc., but there are no side effects and food that can be easily taken orally Many studies on additives and preparations have also been made.

  For example, blood flow promoters such as tocopherol acetate, ginseng, ginger, capsaicin (a compound derived from chili extract) can be mentioned, but these can temporarily increase the body surface temperature, but do not modulate the deep body temperature. Since it cannot be normalized, it did not provide a fundamental solution to lowering body temperature.

  Thus, studies have been conducted on ingesting extracts obtained from various plants, with the aim of normalizing the modulation of deep body temperature. For example, proanthocyanidins extracted from pine bark (patent document 1), quinoa extract (patent document 2), extracts of the genus Hononiku (patent document 3) and the like have been studied. However, these functions were still not sufficient.

JP 2006-143654 A JP 2010-260848 A JP 2011-157302 A

  This invention is made | formed in view of the said conventional situation, The subject is providing the deep body temperature raising agent which raises deep body temperature.

  (1) A deep body temperature increasing agent characterized by containing a black ginger processed article.

  (2) The deep body temperature elevating agent according to (1), wherein the black ginger processed article uses a black ginger rhizome.

According to the present invention, since it has a remarkable effect of increasing the deep body temperature, it is possible to normalize the modulation of the deep body temperature that induces a sustained decrease in body temperature, and return the body temperature of the living body to a normal state. The present invention also relates to diseases such as hypotension, decreased visceral function (constipation / diarrhea), decreased immunity, poor circulation (coldness, stiff shoulders, low back pain, joint pain), sleep disorder, decreased metabolism (obesity), depression, etc. In addition, it can be used for treatment and prevention of diseases caused by persistent hypothermia.

The time-dependent change of the body temperature in the ear of a mouse | mouth is shown. The area under the curve of the intrabody temperature of the mouse is shown. The time-dependent change of the surface body temperature of a mouse | mouth is shown. The area under the curve of the surface temperature of the mouse is shown. The time-dependent change of the brown adipose tissue sympathetic nerve activity of a mouse | mouth is shown.

  Hereinafter, embodiments of the present invention will be described.

  Kaempferia Parviflora is a plant belonging to the genus Gingidae, genus Van turmeric that grows naturally in Southeast Asia. It increases energy, nourishing tonicity, lowering blood sugar level, restoring physical strength, improving digestive system, vaginal zone, hemorrhoids, hemorrhoids, nausea, There are reports of improvement in stomatitis, joint pain, and stomach pain. Black ginger is a natural plant that has been ingested by humans for a long time. The present inventors have found that the various physiological actions of black ginger have an excellent deep body temperature increasing effect, and have completed the present invention.

Unlike elevated body surface temperature alone, deep body temperature increases, resulting in hypotension, decreased visceral function (constipation / diarrhea), decreased immunity, poor circulation (coldness, stiff shoulders, low back pain, joint pain), sleep disorders, metabolism It is possible to treat or prevent diseases such as depression (obesity), depression and the like caused by persistent hypothermia.

  More specifically, the present invention provides the following.

  Bark, roots, leaves, stems, flowers, branches, etc. can be used as black ginger for obtaining the composition of the present invention. Among them, preferred is a rhizome. Specifically, black ginger processed products (dried products, cut products, etc.) or powders, juices or extracts thereof can be used. Here, the extract means an extract obtained by extracting the black ginger or processed product thereof with a solvent, a diluted solution or a concentrated solution thereof, or a dried product thereof and a powder thereof. In consideration of the point of use as food or medicine, it is also preferable to use an extract. In the present invention, the processed article includes all of them.

  Black ginger powder products are washed, dried sliced black ginger using the sun or a dryer, and then processed as it is or cut into an appropriate shape or size using a crusher. It can be obtained by grinding. As the pulverizer, those usually used can be widely used. For example, a pulverizer composed of a raw material hopper, a pulverizer, a classifier, a product holder and the like can be used.

An extract of black ginger is obtained by extracting black ginger or a processed product thereof with a solvent. Examples of the solvent used for extraction include lower alcohols such as ethanol, methanol, isopropanol and butanol, lower esters such as ethyl acetate and methyl acetate, acetone, and a mixture of these with water. Among these, since the composition of the present invention is ingested by humans, it is preferable to use ethanol alone or a mixture with water (so-called hydrous ethanol). In particular, it is preferable to use a solvent containing ethanol at a concentration of 40% or more.

When a mixture is used as the solvent, for example, an acetone / water (2/8 to 8/2, volume ratio) mixture, an ethanol / water (2/8 to 8/2, volume ratio) mixture, or the like can be used. . In the case of ethanol / water, it is preferable to add a solvent having a mass of 2 to 20 times its mass to the rhizome of black ginger and extract it at room temperature or under heating for 10 minutes to 48 hours.

There is no particular limitation on the extraction method to be used, but it is preferable that the extraction is performed under as mild conditions as possible from the viewpoint of safety and convenience. For example, the raw material plant part or its dried product is crushed, crushed or shredded, 2 to 20 times the mass of solvent is added thereto, and the mixture is allowed to stand and shake for 10 minutes to 48 hours in the range of 0 ° C. to the reflux temperature of the solvent. The extraction is performed under any conditions such as stirring or refluxing. After the extraction operation, separation operations such as filtration and centrifugation are performed to remove insoluble matters. An extract is obtained by diluting and concentrating as necessary. Further, the same operation may be repeated for insoluble matter, and the extract may be used in combination with the previous extract. These extracts may be used after further purification by a purification method commonly used by those skilled in the art.

  The deep body temperature increasing agent of the present invention can be used as it is, or as a mixture with other components, as a parenteral administration agent, an oral administration agent or the like, according to the above-mentioned purpose. As parenteral administration agents, intravenous administration agents, intramuscular administration agents, subcutaneous administration agents, transdermal administration agents and the like are used. It is good also as an intraperitoneal administration agent which is one of the subcutaneous administration agents. Moreover, it is also preferable to administer directly to the internal organs by injection etc. as an enteral agent.

  Furthermore, the deep body temperature increasing agent of this invention can also be used as a form suitable for cosmetics. For example, it can be processed into various forms such as lotions, emulsions, gels, creams, ointments and the like. Specifically, it can be used as lotion, cosmetic cream, milky lotion, cream, pack, hair tonic, hair cream, shampoo, hair rinse, treatment, body shampoo, facial cleanser, soap, foundation, hair restorer, aqueous ointment, spray, etc. .

  Although there is a method for parenteral administration from the viewpoint of preventing the degeneration of black ginger components, the components of black ginger are strong enough to withstand extraction with organic solvents and are not easily denatured by exposure to gastric juice. A sufficient effect can also be obtained as an oral administration agent. Examples of the orally administered agent include tablets, granules, powders, and capsules. It is preferable to encapsulate and increase the amount that reaches the internal organs as it is. Furthermore, one agent of the present invention can be supplied in the form of drinks, syrups, and jelly, in addition to those having dosage forms such as tablets, powders, and capsules.

  As an orally administered agent, for example, it is formed into a tablet, granule or the like using additives usually used by those skilled in the art (for example, excipients such as dextrin, starch, sugar, calcium phosphate, fragrance, perfume oil, etc.). Alternatively, it may be dissolved in water, beverage or the like to form a liquid. Preferably, it is in the form of a capsule, granule, tablet or beverage.

  As a method for producing capsules, a conventionally known method for producing soft capsules may be used except that the above plant or extract is used as the contents. Examples of such a production method include a method of encapsulating contents with a rotary filling machine using a capsule film sheet and molding a capsule preparation, or a method of producing a seamless capsule by a dropping method.

  For tablets, add appropriate binders, excipients, disintegrants and lubricants as necessary to the granules containing the plant or the extract or the extract itself, and use a known tableting method. Can be prepared. For the granule, various known wet and dry granulation methods can be applied, and the granule is molded together with an appropriate binder and excipient. Furthermore, drinks, syrups, jellies, etc. can be prepared by adding known sugars, acids, fragrances and the like to adjust the flavor and preparing them by known production methods.

  Although there is no restriction | limiting in particular as a compounding quantity of the black ginger processed article contained in the deep body temperature increasing agent of this invention, If it is an oral administration agent, Preferably it is 0.0001% or more, More preferably, it mix | blends 0.001% or more. In the case of a parenteral administration agent such as cosmetics, it is preferably 0.00001% or more, more preferably 0.0001% or more.

Next, the present invention will be described in more detail based on examples, but the present invention is not limited thereto.

(Confirmation of temperature rise effect)
(1) Test substance The black ginger was obtained by roughly pulverizing the rhizome of Thai black ginger with a miller. For the ginger powder, brown powder from China was used as it was. In both cases, distilled water was used as a solvent at the time of administration, and suspended at 50 mg / mL and 100 mg / mL. Ethanol was used by preparing a 20 (v / v)% solution using distilled water as a solvent.

(2) Experimental animals and breeding method Five groups of 6 ICR male mice of 7 weeks old were prepared as a group, and used for the experiment after a habituation period of 5 days or more. The grouping was performed so that the average value of body weight was almost uniform immediately before the test. During the test, the test substance was administered and fasted until the end of the test.

(3) Administration of test substance One group of ICR male mice was used as a control (distilled water). Groups 2 and 3 were administered with black ginger powder, and for group 2, black ginger powder was orally administered at a dose of 1000 mg / kg once per 500 g / kg. Also, groups 4 and 5 were ginger powder administration groups, and ginger powder was orally administered once per 500 g / kg for group 4, and ginger powder was once administered at 1000 mg / kg for group 5. Table 1 shows each test group and dose. Note that the test substance and ethanol were each forcibly orally administered to a mouse at 10 mL / kg with a stomach tube.

(4) Body temperature measurement Five minutes after administration of the test substance to the mice, ethanol was intraperitoneally administered at 4000 mg / kg. The body temperature of each part was measured before the start of the test (0 minutes) and immediately after administration (5 minutes), and thereafter the body temperature was measured every 10 minutes up to 60 minutes after the start of 10 minutes. For measuring the body temperature of mice, an animal ear thermometer Pet-Temp (PT-300; Advanced Monitors)
Corporation was used to measure in-ear and surface (back) body temperature.

(5) Results FIG. 1 shows the time-dependent changes in body temperature measured in the ear of the mouse, and FIG. 2 shows the area (AUC) of the body temperature change curve obtained. FIG. 3 shows changes in body temperature measured on the body surface of the mouse, and FIG. 4 shows the area (AUC) of the body temperature change curve obtained.

  Administration of ethanol reduces the body temperature in the ear and surface of the mouse. Regarding the surface temperature, the administration of ginger and ginger has little effect on suppressing the decrease in body temperature. However, with regard to the temperature in the ear, when ginger was administered (Groups 4 and 5), the body temperature decreased, but in black ginger, contrary to ginger, it showed a strong decrease-inhibiting action, and its action was Long lasting (Group 2, 3).

  From the above results, it was confirmed that the intake of black ginger can increase the deep body temperature. On the other hand, ginger known to dilate peripheral blood vessels is considered to have very little or no such effect.

(Examination of cause of temperature rise)
(Manufacture of black ginger extract)
300 g of black ginger rhizome chips are weighed and placed in a triangular flask together with 3 l of 60% ethanol. Allow to stand at room temperature for 24 hours while stirring several times along the way. After filtration under reduced pressure, the remaining chip is dipped again in 3 l of 60% ethanol and left to stand at room temperature for 24 hours for extraction. This was filtered under reduced pressure to obtain a second extract. The first and second extracts were combined and concentrated under reduced pressure to about 1/6 to obtain a stock solution.

(Brown adipocyte tissue activity evaluation test)
Wistar male rats (about 9 weeks old) having a body weight of about 300 g and kept in a constant temperature animal room at 24 ° C. for 1 week or more under a light / dark cycle every 12 hours (lighted from 8:00 to 20:00) were used. On the day of the experiment, after fasting for 3 hours, anesthetized with urethane, inserted a cannula for duodenal administration, then suspended the interscapular brown adipose tissue sympathetic nerve and the femoral cutaneous sympathetic nerve with a silver electrode, Electrical activity was measured. At the time when these measured values settled (around 13:00), 1 ml of a solution obtained by diluting the black ginger extract with 60% ethanol to a dose of 500 mg / kg was diluted 100 times with 60% ethanol. These changes in autonomic nervous activity were measured electrophysiologically. As a control experiment, 1 ml of a 60% ethanol solution as a solvent was administered into the duodenum. A tube was inserted into the trachea from the start of surgery to the end of measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a heat retaining device. The data of autonomic nerve activity was analyzed by the average value of the firing frequency per 5 seconds (pulse / 5s) every 5 minutes, and expressed as a percentage with the value before the start of stimulation (0 minute value) as 100%.

  FIG. 5 shows the time course of interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in mice. The duodenal administration of 1 ml of a 60% ethanol solution performed as a control experiment first gradually decreased BAT-SNA, decreased BAT-SNA to the lowest value of 74.4% 25 minutes after administration, and then gradually increased BAT-SNA. In 60 minutes after the administration, BAT-SNA was recovered to 101.7%. In contrast, the duodenal administration of 1 ml of a 100-fold diluted solution of the stock solution (including 5 mg / kg equivalent) reduced BAT-SNA to 70.2% 15 minutes after administration. However, BAT-SNA was gradually increased gradually and increased to 176.7% 60 minutes after administration.

  From the above experimental results, the duodenum administration of the black ginger extract increases the activity of interscapular brown adipose tissue and raises the deep body temperature compared with the 60% ethanol solution administration as a control experiment I understood.

Furthermore, using the black ginger extract powder, the black ginger pulverized product, and the black ginger extract obtained by drying the black ginger extract obtained by the above method, beverages, granules, soft capsules, cosmetic liquids, shampoos, soaps are formulated according to the following table. It was created.
(Manufacture of crushed black ginger)
After washing the black ginger rhizome, it was sliced to about 1 to 10 mm and dried in the sun for one day. Then, it dried for 4 to 6 hours with the oven dryer set to 40-100 degreeC, and sterilized at 130-200 degreeC for 5 to 20 second after coarse grinding. The sterilized coarsely pulverized product was pulverized by a pulverizer to obtain a black ginger pulverized product.
(Manufacture of black ginger stems, leaves, and pulverized flowers)
By the same method as above, a black ginger stem pulverized product, a leaf pulverized product, and a flower pulverized product were obtained.

Example 1 (Manufacture of a liquid agent)
Each component was blended at the blending ratio in Table 2 to obtain a liquid.

Example 2 (Production of granules 1)
According to Table 3, sucralose 0.5 kg, citric acid 5 kg, reduced maltose starch syrup 64.5 kg, indigestible dextrin 67.2 kg, licorice extract 0.5 kg, black ginger ground product 16.8 kg, cyclodextrin 8.4 kg, shoyaku 5 kg is charged into a flow coater NFLO-200 fluidized bed granulator (manufactured by Freund Sangyo Co., Ltd.) and mixed with an air stream for several minutes. This was granulated by spraying 2000 mL of water for 1 minute. Subsequently, the obtained granulated product was sieved with a 30-mesh sieve to obtain granules.

Example 3 (Production of granules 2)
In the same manner as in Example 2, the ingredients shown in Table 4 were blended to prepare granules.

Example 4 (Production of soft capsule 1)
The content liquid blended at the blending ratio shown in Table 5 was prepared, and the capsule film blended at the blending ratio shown in Table 6 was filled into soft capsules. Encapsulation was performed by casting a capsule coating solution to form a film, filling the content solution inside, heat-sealing, and drying the formed soft capsule.

Example 5 (Production of soft capsule 2)
The content liquid blended at the blending ratio shown in Table 7 was prepared, and the capsule film blended at the blending ratio shown in Table 8 was filled into soft capsules as in Example 4.

Example 6 (Manufacture of serum)
Each component was blended at the blending ratios shown in Table 9 to obtain a cosmetic liquid.

Example 7 (Production of shampoo)
Each component was mix | blended with the mixture ratio of Table 10, and it was set as the shampoo.

Example 8 (Manufacture of soap)
Each component was blended at a blending ratio shown in Table 11 to obtain a soap.

Claims (1)

A processed body of black ginger, the processed body of black ginger contains an ethanol extract of black ginger rhizome , and the ethanol extract is an extract of ethanol alone or water-containing ethanol. Agent.

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